of the humanized anti GD2 antibody hu3F8 when combined with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in patients with high risk neuroblastoma. All observed adverse events, regardless of treatment group or suspected causal relationship to study drug will be recorded. Adverse events will be identified and graded using the Common Toxicity Criteria Version 4.0

Secondary Outcome Measures:

pharmacokinetics of hu3F8 [ Time Frame: 1 year ] [ Designated as safety issue: No ]

when combined with GM-CSF. Pharmacokinetics will be measured by serial blood sampling following the first two iv doses of hu3F8 as listed in Table 3. Serum hu3F8 will be measured pre-infusion and at time pre- (within an hour before hu3F8), 5 min, 3h, 6-8h, 24h, 48h, 72h, 96, 120h, 168h 216h and 264h after the first infusion of hu3F8 during cycle1 and, whenever possible, peak hu3F8 level at pre- and ~5 minutes post-infusion will also be measured for each dose of hu3F8 in subsequent cycles .

Another secondary objective is to assess the anti-tumor activity of hu3F8 against NB and other GD2-positive tumors. Anti-tumor activity will be measured by international neuroblastoma response criteria (INRC).

quantitate the response of marrow NB [ Time Frame: 1 year ] [ Designated as safety issue: No ]

will be measured using quantitative Reverse transcription-PCR (qRTPCR) and its relationship with dosage of hu3F8 explored.

This phase I single arm trial assesses escalating doses of iv hu3F8 (days 1, 3, 5) in the presence of sc GM-CSF (day -4 through 5). These 3 doses of hu3F8 and 10 days of GM-CSF constitute a treatment cycle.

Biological: Hu3F8 With GM-CSF

One cycle consists of treatment with hu3F8 for 3 days (day 1, 3 and 5). GM-CSF is started 5 days in advance of each hu3F8 cycle at 250 mcg/m2/day (day -4 to day 0), and at 500 mcg/m2/day x 5 days (day 1 to day 5). Cycles are 5 days. Cycles are repeated at 2-4 week intervals between first days of hu3F8, through 4 cycles. Patients who complete 4 cycles of treatment without complications or disease progression have the option of continuing treatment for up to 24 months from their first dose of hu3F8.

Eligibility

Ages Eligible for Study:

1 Year and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Diagnosis of NB as defined by a) histopathology (confirmed by the MSKCC Department of Pathology), or b) BM metastases or MIBG-avid lesion(s) plus high urine catecholamine levels.

Patients must have either refractory or relapsed high-risk NB (including MYCNamplified stage 2/3/4/4S of any age and MYCN-nonamplified stage 4 in patients greater than 18 months of age) resistant to standard therapy*.

*For NB, standard therapy includes intensive induction chemotherapy, followed by a variety of consolidation or salvage therapies, depending on response.

No chemotherapy or immunotherapy for a minimum of three weeks prior to study enrollment

Women of child-bearing potential must be willing to practice an effective method of birth control while on treatment

Signed informed consent indicating awareness of the investigational nature of this program.

Exclusion Criteria:

Existing major organ dysfunction > grade 2, with the exception of hearing loss and hematologic toxicity (defined as suppression of all subtypes of WBCs, RBCs, and platelets).

Active life-threatening infection.

Pregnant women or women who are breast-feeding.

Inability to comply with protocol requirements, including PK studies and genetic studies.

History of allergy to mouse proteins.

Human anti-hu3F8 antibody (HAHA) titer >1300 Elisa units/ml.

History of allergy to GM-CSF

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01757626